C2B8 is chimeric anti CD20 antibody with human constant regions and murine antigen recognition sequences. It has high affinity for B cells and most B cell lymphomas. This trial compares C2B8 alone and C2B8 plus interferon-alpha in the therapy of recurrent B cell lymphomas. It has completed accrual. Eleven patients have been treated with antibody alone. Two patients with mantle cell lymphoma experienced temporary responses but progressed after two months. Five patients with follicular lymphomas have had responses to treatment (three complete and two partial). One patient with follicular large cell non-Hodkin's lymphoma (an intermediate grade tumor) had a dramatic CR which has lasted for greater than twelve months. The overall response rate is consistent with prior studies and the experience at other institutions, confirming the therapeutic promise that this drug carries. The mediation response duration is 3 months, but this is skewed by the patients with mantle cell lymphoma, a disease with a very poor prognosis which has since been excluded from the trials. There has been no evidence of signficant toxicity at our institution. Thirteen patients have been treated with combined interferon-alpha and C2B8. Eight patients requried discontinuation or dose reduction of the interferon due to signficiant toxicity. The toxicities associated with the first infusion of the antibody (fever, chills and orthostatic hypotension) may have been augmented by the simultaneous administration of the immune modulating agent. Responses so far include six partial readmissions and one complete response (a total response rate of 58%) with a maximal duration of 24+ months and a mediation duration of response of three months. It was noted that several patients experienced rapid disease progression while taking interferon but appeared to responsd well to the antibody infusions. These patients did not experience an overall response. We subsequently have treated them with a course of antibody alone to determine whether they might respond in the absence of the interferon. Neither patient experienced signficant benefit from this second course of therapy.